Renal dysfunction or failure and, in particular, end-stage renal disease, causes the body to lose the ability to remove water and minerals and excrete harmful metabolites, maintain acid-base balance and control electrolyte and mineral concentrations within physiological ranges. Toxic uremic waste metabolites including urea, creatinine, and uric acid accumulate in the body's tissues, which can result in a person's death if the filtration function of the kidney is not replaced.
Dialysis is commonly used to replace kidney function by removing these waste toxins and excess water. In one type of dialysis treatment—hemodialysis—toxins are filtered from a patient's blood externally in a hemodialysis machine. Blood passes from the patient through a dialyzer separated by a semi-permeable membrane from a large volume of externally-supplied dialysis solution. Typically, the blood passes through the inside of semi-permeable hollow fibers, and the dialysis solution (dialysate) flows on the outside of the semi-permeable hollow fibers in a countercurrent direction. The waste and toxins dialyze out of the blood through the semi-permeable membrane into the dialysis solution, which can then be discarded.
The patient's blood is typically exposed to intravenous cannulas, tubing, drip chambers, headers, potting compound, and dialysis membranes during the dialysis procedure. These surfaces exhibit a variable degree of thrombogenicity and can initiate clotting of blood, especially in conjunction with exposure of blood to air in drip chambers. The resulting thrombus formation may be significant enough to cause occlusion and malfunction of the extracorporeal circuit. See J. T. Daugirdas, P. G. Blake, and T. S. Ing, Handbook of Dialysis, (2007).
One method of preventing blood clotting is to administer an anticoagulant, typically heparin, to the patient, shortly before or during the dialysis treatment. Heparin, however, has potential undesirable side effects, such as, for example, pruritus, allergy, osteoporosis, hyperlipidemia, heparin-induced thrombocytopenia (HIT), and excessive bleeding. Heparin is therefore not recommended for patients at risk of bleeding due to gastrointestinal lesions (gastritis, peptic ulcer, angiodysplasia), recent surgery, or pericarditis.
Another method of preventing blood clotting is by regional citrate anticoagulation (RCA), which can be used alone or combined with potentially reduced heparin administration, as shown in FIG. 1. Id. at p. 221. The application of RCA in hemodialysis typically involves infusion of citrate (e.g., trisodium citrate) before the hemodialyzer, which complexes with ionized calcium (iCa) in the blood and thereby interferes with the blood coagulation cascade by removing calcium (formerly known as factor IV) from the blood, preventing the blood from clotting, followed by calcium infusion after the dialyzer. The extremely low ionized calcium levels generated by infusion of citrate into the arterial line prevent clotting in the extracorporeal circuit but have to be raised again in the venous line before the blood re-enters the patient's systemic circulation. Citrate infusion and calcium replacement have to be balanced carefully to avoid systemic hypo- or hypercalcemia in the patient. See U.S. application Ser. No. 12/580,803, entitled “Method Of Determining A Phosphorus Binder Dosage For A Dialysis Patient,” filed on Oct. 16, 2009. This balance is typically achieved by close monitoring of systemic iCa levels, which is generally accomplished by repetitive blood draws and iCa measurements throughout the dialysis treatment. This is a labor- and material-intensive process and, hence, an undesirable cost factor. Furthermore, the introduction of citrate into the blood is not recommended for patients with liver disease, due to their diminished ability to process free citrate and citrate-calcium complexes.
Therefore, there is a need for a method of preventing blood from clotting in an extracorporeal blood treatment system without addition of an anticoagulant into the blood.